Chapter 9- Cellular Respiration NOTES

The focus of this chapter is to learn how cells can harvest chemical energy stored in organic molecules to generate (or regenerate) ATP.

All energy here on earth ultimately comes to the earth via the sun, and leaves as heat.

9.1 Catabolic pathways- Cells degrade complex (high energy) molecules to waste products (low energy). This breakdown produces energy for work and releases heat.

2 pathways:1. Cellular Respiration - EFFICIENT, REQUIRES OXYGEN!! 2. Fermentation- Not efficient, but NO OXYGEN requirement (anaerobic)

Overall we can sum up these reactions as-Organic compounds + O2 CO2 + H2O + Energy

Specifically we will be looking at cellular respiration *KNOW EQUATION BELOW!

C6H12O6 + 6O2 6CO2 + 6H2O + Energy (ATP and heat)ΔG = -686 kcal/mol (used to form ATP)

REDOX Reactions *Khan Academy- specific to redox in C.R.Like most chemical reactions, electrons are transferred in the process of breaking bond and reforming new bonds. These reactions are called REDOX (reduction/oxidation) reactions.

They are based on the transfer of electrons from reactants to products. *O.I.L. R.I.Go Oxidation = LOSS of electronso Reduction = GAIN of electronso Electron acceptor = Oxidizing agent (the chemical being REDUCED; GAINING e-)o Electron donor = Reducing agent (the chemical being OXIDIZED; LOSING e-)

OXYGEN is one of the BEST OXIDIZERS because of its strong electronegativity!

- As electrons MOVE CLOSER to HIGHLY electronegative atoms, it PRODUCES energy- As electrons MOVE FURTHER AWAY from highly electronegative atoms REQUIRES energy.

Overall in cellular respiration->glucose is oxidized, and oxygen is reduced.

(*Therefore, glucose is the reducing agent and oxygen is the OXIDIZING AGENT!)

Breaking down Glucose for Energy release:Molecules with many H (such as carbs and fats i.e. long hydrocarbon chains) are great reserves of potential energy, but this release must be controlled.

- Glucose must be broken down in multiple steps- all driven by enzymes.

3 MAIN STEPS: Glycolysis, Citric Acid Cycle, Oxidative Phosphorylation

Electrons carriers help facilitate a flow release of energy: NADH and FADH2 (electron shuttles)

Formation of NADH (example of a redox reaction)= 2 electrons are stripped from substrate (food) by the enzyme dehydrogenase (along with two protons) and are then passed to the molecule NAD+ (electron acceptor) and forms NADH *FULL CAR w/ 2 e- One proton is lost as H+ to the surrounding.

Overview of cellular respiration- *KNOW REACTANTS/PRODUCTS of EACH STAGE!1) Glycolysis: In cytosol. 1 Glucose 2 pyruvate. NO oxygen is needed. 2) Citric acid Cycle (AKA Krebs Cycle (KC): In mitochondria. Some ATP and CO2 produced. 3) Oxidative phosphorylation- In mitochondria By ETC and chemiosmosis

Glycolysis and KC are both catabolic process that decompose glucose and other organic molecules

90% of ATP produced is done so in the ETC by oxidative phosphorylation There is some ATP produced in glycolysis and KC but by substrate level phosphorylation. Overall, cellular respiration PRODUCES 38 molecules of ATP from a SINGLE GLUCOSE!

STAGE #1: Glycolysis. *Animation Harvest chemical energy by oxidizing glucose to pyruvate. Net gain of 2 ATP and 2 NADH molecules.

- A six C sugar is broken into two, three C sugars.

These electrons are eventually going to end up with O2, but how? (MAIN OXIDIZING AGENT!)Electron transport chain (ETC) located in the mitochondria. This “chain” is a controlled release of energy.

Electron transfer from NADH to O2 is exergonic and produces -53 kcal/mol of energy. - The overall electron flow=. Food NADH ETC O2

- No CO2 is produced, because no O2 is being used. 1) Energy investment stage- 2 ATP are used2) Energy payoff stage- 4 ATP and 2 NADH produced (NET GAIN = 2)

Energy investment stage- 1) Glucose is phosphorylated2) Glucose is then turned to fructose3) Fructose is then phosphorylated 4) The enzyme aldolase splits the sugar into two sugars

Energy payoff stage- 1) 2 NADH produced (very exergonic) and uses the energy to attach a random

phosphate to each substrate. 2) 2 ATP produced3) The molecule is rearranged to make unstable4) 2 more ATP produced5) End result are two pyruvate molecules

******************************************************************************STAGE #2: Citric Acid Cycle (AKA The Krebs Cycle). *Animation

If we look at EACH individual TURN of the cycle, we produce-1) 3 CO2

2) 1 ATP3) 4 NADH4) 1 FADH2

This cycle REQUIRES oxygen to take place

****PAUSE! INTERMEDIATE STEP REQUIRED!!!**** STAGE 1.5?!?

Conversion of Acetyl CoA:Before we enter the actual cycle, there is one intermediate step that must take place = the conversion of the pyruvate into Acetyl CoEnzyme A (Acetyl CoA).

How this happens:1) Our pyruvate loses 1 molecule of C (oxidation), and 1 molecule of CO2 is released2) NAD+ is reduced to NADH and released3) CoEnzyme A then attaches to our 2 C molecule- making it VERY unstable and

reactive.NOW…….we enter the actual KREBS CYCLE (STAGE #2)

Krebs Cycle= an 8 step cycle, each step is driven by the work of enzymes.

- Our Acetyl CoA (2C) molecule that was synthesized above, ENTERS the cycle and bonds with an Oxaloacetate molecule (4C). This bond forms the molecule citrate (6C). The rest of the cycle contains steps that break down the citrate molecule in order to reform Oxaloacetate molecule (4C).

Process for the intermediate step before Krebs Cycle

PRODUCTS OF THE KREBS CYCLE: *one turn 2 Molecules of CO2 (+1 CO2 from earlier Acetyl CoA part = 3 CO2) 3 molecules of NAD+ are reduced to NADH

(+1 NADH from earlier Acetyl CoA part = 4 NADH) 1 ATP through substrate level phosphorylation 1 molecule of FADH2 (this molecule is another electron carrier- similar to NADH)

******************************************************************************STAGE #3: Oxidative Phosphorylation and the Electron Transport Chain (ETC) *Animation

So far- only 4 ATP have been produced! The remnants of our glucose are tied up in the Krebs cycle. So, what is left that can still make ATP? NADH and FADH2

Electron Transport Chain: located in a series of molecules embedded in the inner membrane of the mitochondria. *KNOW LOCATIONS!** Increase the surface area of the mitochondria increase the amount of ATP that can be produced. Folds called cristae inside of the mitochondria increase the surface area of the mitochondria**

The ETC is made up of multiple protein complexes, numbered from I-IV. Typically these proteins require prosthetic groups i.e. cofactors that assist in their

function (like cytochrome C oxidase require Fe+). These proteins accept/donate electrons down the energy gradient by being constantly

reduced/oxidized. *ELECTRON TRANPORT CHAIN = Moves e- down the line by oxidize-reduced-oxidized-reduced….etc.

How does the ETC function? NADH donates its electrons to the first protein in the ETC, called flavoprotein.

*Drops off e- (shuttles e-) The electrons are then passed to the rest of the molecules of the ETC. The last

electron carrier (Cytochome a3) then donates its electrons to the final electron acceptor---OXYGEN. This donation attracts H+ which then attach, forming our final product= H2O.

SO, WHERE’S THE ATP COME IN?!?!

The job of the ETC is to “break the fall” of electrons, as they strive to reach their final acceptor (oxygen). Then…. CHEMIOSMOSIS is how ATP is produced. (Still Stage #3)

CHEMIOSMOSIS: Embedded inside of the INNER mitochondrial membrane, proteins called ATP synthase (these are the enzymes that make ADP ATP). These proteins are very similar to an ion pump working in reverse.

Uses an existing H+ ion concentration gradient to drive the synthesis of ATP (also can be thought of as a pH gradient because we know that pH is directly related to the concentration of H+)*

This is similar to a waterwheel- uses the fall of water to turn a wheel and power something. *or a turbine

Why the H+ gradient? As the enzymes of the ETC accept/release H+ along with the pathway, e- attact H+ to pass through (opposite charges attract!) H+ are dragged into the intermembrane space of the mitochondria = HIGH concentration of H+ in the intermembrane space, which want to flow to the LOWER concentration in the mito. matrix *DOWN THEIR GRADIENT! (called a proton-motive force). DRIVES THE ATP SYNTHASE TO TURN AND CHARGE UP ADP to ATP!

Overall the flow of electrons is: Food (glucose) NADH ETC proton motive force ATP- Each NADH produces about 3 ATP- Each FADH2 produces about 1.5 - 2 ATP

TOTAL RELEASE = 32-34 ATPS

HIGH [H+]

LOW [H+]

Cellular Respiration converts about 40% of the energy stored in glucose to energy stored in the form of ATP (this is considered to be a very effective conservation of energy). The rest of the energy is LOST in the form of heat!

ANAEROBIC ENERGY RELEASE : FERMENTATION

Fermentation- Production of ATP when there is NO OXYGEN present. Two overall types of fermentation:

1. Alcoholic Fermentation2. Lactic Acid Fermentation

*STARTS OFF THE SAME as C.R. -> WITH Glycolysis. - Produces two ATP, whether or not oxygen is present (by means of substrate level

phosphorylation). However, if no oxygen is present, then pyruvate cannot enter the preliminary steps of the citric acid cycle.

- NAD+ HAS to be present to oxidize (accept electrons) from the intermediate molecules of glycolysis. But what does the NADH do with these electrons once it has them and cannot pass them on to the ETC? It gives the electrons BACK to the pyruvate (or derivative molecule) in order to reform NAD+.

1) Alcoholic fermentation: Common in bacteria and yeast. *YEAST Animation. TED Ed animation - Fermentation Pyruvate is converted to ethanol (ethyl alcohol) in two steps:

o 2 molecules of pyruvate each lose a carbon in the form of CO2 (released) and is now considered acetalaldehyde.

o The acetalaldehyde then is reduced by the two NADHs that were produced early in glycolysis and form ethanol

2) Lactic Acid Fermentation Bacteria and animal muscles cells (temporarily- when oxygen levels are low.) Pyruvate is reduced directly to lactate by NADHs giving up their electrons.

Fermentation vs. Cellular Respiration - *REVIEW Animation Glycolysis and cellular respiration BOTH use NAD+ the oxidizing agent that accepts electrons.

o In fermentation, the final electron acceptor is an organic molecule (such as pyruvate in lactic acid fermentation)

o In cellular respiration, the final electron acceptor is OXYGEN!!

Cellular respiration is clearly more efficient than fermentation (38 ATP vs. 2 ATP) Anaerobic bacteria still successfully produce enough energy in order to survive.

o Facultative anaerobes can live in either condition (aerobic and anaerobic) and successfully produce ATP for survival.

o In the early atmosphere there was no oxygen present, so it is thought that all organisms only used glycolysis and fermentation in order to produce energy.

o Glycolysis is the most widespread metabolic pathway which signifies that it developed early in the earth’s history.

How do we process other energy sources BESIDES GLUCOSE (carbs)?- Other metabolic pathways exist, but must be modified before entering C.R.- Almost all digestible organic molecule we eat CAN be used for energy!

Large carbohydrates can easily be converted to glucose by enzymes, then enter glycolysis.

Proteins (Amino Acids) can be “deaminated” (amino groups removed) and then can enter as intermediate molecules in glycolysis and the citric acid cycle.

Lipids- Beta oxidation breaks fatty acids down into two-carbon fragments which can enter cellular respiration as acetyl CoA.

REGULATION OF THE BIOSYNTHESIS and ATP PRODUCTION- Almost every molecule commonly used in the body can be produced by “biosynthesis”. - Supply and demand decides what needs to be built and what is not any longer needed

(feedback inhibition).

Phosphofructokinase: One important enzyme in regulation of the production of ATP- controls the speed of glycolysis - However, both ATP and citrate are both inhibitors that prevent phosphofructokinase from

functioning. - When ATP and citrate levels are LOW (possibly during strenuous activity or high use of ATP), the

enzyme functions and production of ATP proceeds.- When ATP and citrate levels are HIGH (active CR production), the enzyme inhibits glycolysis and

shuts off the further production of ATP. **Conserves wasted energy if not needed

QUIZ PRACTICE! Game #1Game #2